effect of E1 on D. We can estimate this quantity by excluding all post-morbid measurements of the risk factor from the risk factor GWAS. This allows us to circumvent reverse causation, at the cost of a small decrease in sample size. If D is uncommon, then modification of behavior after onset of D will account for only a small fraction of the population variance in E1, so the effect of reverse causation on the genetic correlation will be small. Thus, reverse causation is primarily a concern for high-prevalence diseases.
